Recent investigations have suggested that preoperative chemoradiation may offer improved local control in patients with resectable adenocarcinoma of the pancreatic head. However, current chemoradiation protocols are characterized by poor response rates and no instances of complete tumor regression. It is now apparent that the resistance of many human malignancies to the effects Of chemoradiation may be due to protective cell cycle responses following DNA damage. Recent investigations have demonstrated that taxol is capable of altering the cell cycle response to DNA damage in pancreatic adenocarcinoma cells, and also to induce apoptosis. Thus taxol-baeed chemoradiation may provide a novel mechanism for manipulating the cell cycle in pancreatic cancer cells, thereby allowing for effective tumor downsizing prior to surgery. A recent phase I study of taxol-based chemoradiation in patients with unresectable pancreatic cancer suggested a response rate approaching 30%, far greater than that observed with previous fluorouracil (5FLJ)based protocols. We therefore propose to investigate taxol-baeed chemoradiation in patients with potentially resectable adenocarcinoma of the pancreatic head under the auspices of a Phase III clinical trial. This proposed study emphasizes strict pre-treatment staging to include only those patients with localized, resectable disease, as well as careful assessment of treatment response using radiographic (i.e. CT, endoscopic ultrasound), metabolic (FDG- PET scanning), and molecular techniques (TUNEL assay for treatment-induced apoptosis).